Nystuen Kaden L, McNamee Shannon M, Akula Monica, Holton Kristina M, DeAngelis Margaret M, Haider Neena B
Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Bioengineering (Basel). 2024 Jan 1;11(1):45. doi: 10.3390/bioengineering11010045.
Alzheimer's Disease (AD) is a complex neurodegenerative disease resulting in progressive loss of memory, language and motor abilities caused by cortical and hippocampal degeneration. This review captures the landscape of understanding of AD pathology, diagnostics, and current therapies. Two major mechanisms direct AD pathology: (1) accumulation of amyloid β (Aβ) plaque and (2) tau-derived neurofibrillary tangles (NFT). The most common variants in the Aβ pathway in , and are largely responsible for early-onset AD (EOAD), while , , and have a modifying effect on late-onset AD (LOAD). More recent studies implicate chaperone proteins and Aβ degrading proteins in AD. Several tests, such as cognitive function, brain imaging, and cerebral spinal fluid (CSF) and blood tests, are used for AD diagnosis. Additionally, several biomarkers seem to have a unique AD specific combination of expression and could potentially be used in improved, less invasive diagnostics. In addition to genetic perturbations, environmental influences, such as altered gut microbiome signatures, affect AD. Effective AD treatments have been challenging to develop. Currently, there are several FDA approved drugs (cholinesterase inhibitors, Aß-targeting antibodies and an NMDA antagonist) that could mitigate AD rate of decline and symptoms of distress.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，由于皮质和海马体退化导致记忆、语言和运动能力逐渐丧失。本综述涵盖了对AD病理学、诊断方法和当前治疗手段的理解情况。有两种主要机制主导AD的病理过程：（1）淀粉样β蛋白（Aβ）斑块的积累，以及（2）tau蛋白衍生的神经原纤维缠结（NFT）。在Aβ途径中， 、 和 中最常见的变异在很大程度上导致早发性AD（EOAD），而 、 、 和 对晚发性AD（LOAD）具有修饰作用。最近的研究表明伴侣蛋白和Aβ降解蛋白与AD有关。几种检测方法，如认知功能、脑成像、脑脊液（CSF）和血液检测，被用于AD的诊断。此外，几种生物标志物似乎具有独特的AD特异性表达组合，可能用于改进的、侵入性较小的诊断。除了基因干扰外，环境影响，如肠道微生物群特征的改变，也会影响AD。开发有效的AD治疗方法一直具有挑战性。目前，有几种获得美国食品药品监督管理局（FDA）批准的药物（胆碱酯酶抑制剂、靶向Aβ的抗体和一种N-甲基-D-天冬氨酸（NMDA）拮抗剂）可以减缓AD的衰退速度并缓解痛苦症状。
